Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

Herpes Simplex Virus Keratitis Reactivation after SARS-CoV-2 BNT162b2 mRNA Vaccination: A Report of Two Cases.

PURPOSE: To report two cases of herpes simplex virus keratitis reactivation following Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccination. METHODS: Two patients (one male, age 42 years, and one female, age 29 years) who are known to have herpetic keratitis presented to our emergency room in a time frame between 4 days and 4 weeks of receiving the vaccine. One patient presented with necrotizing stromal keratitis; the other presented with endotheliitis and epithelial keratitis. PCR for herpes simplex virus (HSV) was obtained from the two patients, and all cases received systemic acyclovir. RESULTS: PCR for HSV came positive in both cases. Patients responded well to the provided treatment. CONCLUSION: Ocular herpetic infection may be activated by COVID-19 (BNT162b2) mRNA vaccine. Treating physician should be alert to such associations, and patients should be followed closely. No direct causality has been proven, but further reporting and investigating similar conditions is recommended.

Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II-IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group.

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.

Risk of hepatitis B virus reactivation following ruxolitinib treatment in patients with myeloproliferative neoplasms.

Objectives The aim of this retrospective analysis was to assess the incidence of hepatitis B virus (HBV) reactivation among patients with myeloproliferative neoplasms (MPN) during and after ruxolitinib treatment. Methods Between February 2013 and February 2020, 224 patients with MPN were treated using ruxolitinib at Peking Union Medical College Hospital. Of these, 6 had chronic, and 56 had resolved HBV infection, including 43 patients who received combination treatment with thalidomide, prednisone, and stanozolol (TSP) during ruxolitinib treatment. Results Two patients with chronic HBV infection who did not take any antiviral prophylaxis developed HBV reactivation and hepatitis flare. The other four patients with chronic HBV infection, who took antiviral prophylaxis before ruxolitinib treatment, did not develop HBV reactivation. Also, no patients with resolved HBV infection received antiviral prophylaxis and developed HBV reactivation. Conclusion This study demonstrated that HBV reactivation and hepatitis flare might commonly occur a few months after initiating ruxolitinib treatment in patients with chronic HBV infection who did not take antiviral prophylaxis, especially in combination with TSP. Still, it was extremely rare in patients with resolved HBV infection.

Reactivations of Latent Viral Infections Are Associated with an Increased Thr389 p70S6k Phosphorylation in Peripheral Lymphocytes of Renal Transplant Recipients.

Reactivations of BK polyoma virus (BKPyV) and human cytomegalovirus (HCMV) frequently cause life- and graft-threatening complications after renal transplantation. Both viruses are dependent on the mTOR pathway for replication. In this study we investigated the association of viral replication with mTOR activity in peripheral lymphocytes of renal transplant recipients. A flow-cytometry based assay for the measurement of Thr389 p70S6k phosphorylation, a surrogate marker of the mTOR pathway was established. Forty-eight adult renal transplant recipients were recruited to measure p70S6k activity in their peripheral blood mononuclear cells. This data set in conjunction with information concerning previous replication of BKPyV and HCMV was examined for correlations. Episodes of BKPyV replication were significantly associated with increased p70S6k phosphorylation in CD4+ T lymphocytes (p = 0.0002) and CD19+ B lymphocytes (p = 0.0073). HCMV infection of patients with a high-risk HCMV constellation of donor and recipient (D+/R-) was associated with increased p70S6k phosphorylation in CD19+ B lymphocytes (p = 0.0325). These associations were found to be independent of the trough levels of the immunosuppressive drugs. Conclusion: P70S6k phosphorylation in peripheral lymphocytes is associated with BKPyV reactivations and to a lesser extent with HCMV infections in renal transplant recipients.

Presumed Herpes Zoster Ophthalmicus Reactivation Following Recombinant Zoster Vaccination.

PURPOSE: To report a case of herpes zoster ophthalmicus (HZO) reactivation after recombinant zoster vaccination. METHODS: A 78-year-old woman, with a history of HZO 20 years ago, was referred for progressive corneal thinning in her left eye that started 1 week after her second dose of recombinant zoster vaccination. RESULTS: At presentation, visual acuity was counting fingers. Corneal sensation was markedly decreased. Slit lamp examination revealed a temporal paracentral epithelial defect 1.5 × 2.0 mm in size with 40% thinning and surrounding stromal inflammation suggestive of stromal keratitis with ulceration. The patient was started on oral valacyclovir, topical erythromycin ointment, and hourly topical lubrication. A bandage contact lens was placed and was replaced 1 week later with self-retained cryopreserved amniotic membrane ring. The ring was removed in the following week when the thinned area was epithelialized with no further evidence of stromal lysis. CONCLUSIONS: HZO reactivation after recombinant zoster vaccination is uncommon but possible. Ophthalmologists should remain aware of potential risks of zoster vaccination and take special precautions in patients with HZO history.

Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia.

BACKGROUND: SARS-CoV-2 pandemic has posed formidable public health and clinical challenges. The use of immunosuppressive agents, such as high dose corticosteroids and cytokine inhibitors (e.g., Tocilizumab) has been suggested to contrast the hyperinflammatory process involved in the pathogenesis of the severe disease, with conflicting evidence. Among the drawbacks of immunosuppressive therapy, the risk of reactivation of latent infections, including parasitic infestations, is to be considered. CASE PRESENTATION: We report a case of a 59-year-old Italian patient treated with high dose intravenous dexamethasone and two intravenous doses of Tocilizumab for interstitial bilateral pneumonia associated with SARS-CoV-2 infection who developed itching, abdominal pain, and an increased eosinophil count. Stool examination confirmed the presence of S. stercoralis larvae. The patient was treated with a 4-day course of Ivermectin with full recovery. DISCUSSION: We report the first case of S. stercoralis infection following an 11-day treatment with high-dose steroids and Tocilizumab for severe COVID-19. Clinicians should be aware of the risk of strongyloidiasis as a complication of the treatment for severe COVID-19.

Risk Factors for Cytomegalovirus Reactivation in Lung Transplant Recipients.

PURPOSE: We examined risk factors that may have contributed to Cytomegalovirus (CMV) reactivation among patients who underwent lung transplantation (LTx). METHODS: We reviewed medical records of patients who underwent LTx at a tertiary healthcare hospital in South Korea between January 2013 and May 2017. We excluded patients who died within the first year after LTx and those lost to follow-up. CMV reactivation was defined as the detection of CMV titers above 3000 copies/ml regardless of specific symptoms after prophylaxis cessation. RESULTS: Of 89 patients included, 39 (43.8%) developed CMV reactivation. Of those 39 patients, 16 (41.0%) experienced additional CMV reactivation. Multivariate analysis identified lymphocyte counts below 1.0 × 103/µl (hazard ratio [HR] 49.33, p < 0.001) and use of steroids at more than twice the standard dose (HR 8.07, p < 0.001) as risk factors for CMV reactivation. The multivariate model also identified chronic kidney disease (CKD; HR 5.19, p = 0.016) and pneumonia (HR 17.22, p = 0.013) as risk factors for repetitive CMV reactivation. CONCLUSION: This study suggests that lymphopenia and high doses of steroids may be important risk factors for CMV reactivation in LTx patients. Our results also suggest that repetitive CMV reactivation may be associated with CKD and pneumonia.

Etiology and therapy of delayed facial paralysis after middle ear surgery.

PURPOSE: This review focuses on the etiology, incidence and therapy of delayed paralysis of the facial nerve (DFP) after different types of middle ear surgery. METHODS: Retrospective review of studies published in English from 1970 until 2019 reporting DFP after tympanoplasty, tympanomastoid surgery, stapedotomy and stapedectomy. The search used the databases of PubMed, Scopus and Cochrane Library. Studies reporting from adult patients and DFP onset after 48 h after surgery were included. Studies dealing with iatrogenic or preexisting facial palsy and case reports were excluded. The initial literature search resulted in 52 studies. The relevance of the publications was verified using title, abstract and full-text analysis. Data were analyzed with descriptive statistics using median, simple sum and statistical significance. RESULTS: Ten studies having 12,161 patients could be included in this review. The incidence of DFP after the middle ear surgeries varies between 0.2 and 1.9%. The surgical stress of the middle ear surgeries is the main trigger for the development of DFP and leads to a virus reactivation and/or neuronal edema. Patients with a dehiscence of the facial canal have a significantly higher probability for a DFP. The recommended therapy of DFP based on the data of the therapy of Bell's palsy, consists of the administration of a steroid. For patients having a case history of previous viral infections, an antiviral prophylaxis is recommended. CONCLUSION: Overall, DFP has a very good prognosis, with mostly complete healing with appropriate therapy. Viral reactivation is the most favored genesis of DFP. Immunization or antiviral prophylaxis is recommended to those patients being at risk for a viral reactivation.